Streptococcus agalactiae (Group B Streptococcus or GBS) causes infections in neonates, pregnant and peri-partum women, and nonpregnant adults. The burden of disease has led to interest in designing a protective vaccine including both capsular polysaccharide (CPS) and GBS surface protein antigens. The beta C protein is a surface protein, which elicits protective antibody in animals. For this reason the beta C protein might be an appropriate component of a vaccine. However, some preliminary data suggest that human naturally-acquired antibodies are not protective despite the fact that the human antibodies recognize the same beta C protein epitopes as do protective vaccine-induced animal antibodies. Additionally, some data suggest there may be significant antigenic variation in the beta C protein, as has been seen in other GBS surface proteins including the alpha C protein. This proposal describes experiments aimed at determining whether a difference in antibody affinity for the beta C protein may explain the difference in protective efficacy of human and animal antibodies. A second goal is to assess the degree of antigenic variation in the beta C protein. The results of these studies will guide further investigation of the role of the beta C protein in humoral immunity to GBS and further consideration of this protein as a component of a protective vaccine.